Association Between Right Ventricular Pressure and Serum Levels of Uric Acid and FGF23 Among Cardiac Patients without Pulmonary Arterial Hypertension

AbstractIntroduction:Pulmonary arterial hypertension (PAH) is a complex disease with poor prognosis. Serum uric acid has been proposed as a potentially non-invasive and objective parameter for prognosis and response to therapy.Objectives:To investigate the potent relationship between serum uric acid levels and functional and echocardiographic parameters in children with PAH.Methods:Serum uric acid levels were measured in 34 children with PAH and were correlated with the functional class, 6-minute walk test, and echocardiographic parameters at baseline and at 12 months follow-up.Results:In pediatric PAH patients serum uric acid levels were higher compared with the control subjects (p = 0.001). In the high uric acid group serum uric acid levels were correlated with 6-minute walk test (p = 0.008), and with several echocardiographic parameters, such as pulmonary vascular resistance (p = 0.04), fractional area change (p = 0.05), left ventricle eccentricity index (p = 0.04), right atrial area (p = 0.03), right ventricle myocardial index (p = 0.01), and pericardial effusion (p = 0.001), markers of right ventricular overload and dysfunction.Conclusions:Serum uric acid levels are easy to collect and measure, and correlate with both functional and echocardiographic parameters that reflect right ventricular dysfunction.

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Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension

Journal of the American Heart Association ◽

10.1161/jaha.121.022712 ◽

2021 ◽

Author(s):

Takanori Watanabe ◽

Mariko Ishikawa ◽

Kohtaro Abe ◽

Tomohito Ishikawa ◽

Satomi Imakiire ◽

...

Keyword(s):

Endothelial Cells ◽

Uric Acid ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Systolic Pressure ◽

Pressure Increase ◽

Right Ventricular Systolic Pressure ◽

Ventricular Systolic Pressure ◽

Pulmonary Arterial

Background Recent studies have demonstrated that uric acid (UA) enhances arginase activity, resulting in decreased NO in endothelial cells. However, the role of lung UA in pulmonary arterial hypertension (PAH) remains uncertain. We hypothesized that increased lung UA level contributes to the progression of PAH. Methods and Results In cultured human pulmonary arterial endothelial cells, voltage‐driven urate transporter 1 (URATv1) gene expression was detected, and treatment with UA increased arginase activity. In perfused lung preparations of VEGF receptor blocker (SU5416)/hypoxia/normoxia‐induced PAH model rats, addition of UA induced a greater pressure response than that seen in the control and decreased lung cGMP level. UA‐induced pressor responses were abolished by benzbromarone, a UA transporter inhibitor, or L‐norvaline, an arginase inhibitor. In PAH model rats, induction of hyperuricemia by administering 2% oxonic acid significantly increased lung UA level and induced greater elevation of right ventricular systolic pressure with exacerbation of occlusive neointimal lesions in small pulmonary arteries, compared with nonhyperuricemic PAH rats. Administration of benzbromarone to hyperuricemic PAH rats significantly reduced lung UA levels without changing XOR (xanthine oxidoreductase) activity, and attenuated right ventricular systolic pressure increase and occlusive lesion development. Topiroxostat, a XOR inhibitor, significantly reduced lung XOR activity in PAH rats, with no effects on increase in right ventricular systolic pressure, arterial elastance, and occlusive lesions. XOR‐knockout had no effects on right ventricular systolic pressure increase and arteriolar muscularization in hypoxia‐exposed mice. Conclusions Increased lung UA per se deteriorated PAH, whereas XOR had little impact. The mechanism of increased lung UA may be a novel therapeutic target for PAH complicated with hyperuricemia.

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